Table Of ContentGenomics in Endocrinology
Contemporary Endocrinology
P. Michael Conn, S E
ERIES DITOR
Polycystic Ovary Syndrome: Current Contro- EarlyDiagnosisofEndocrineDiseases,editedby
versies, from the Ovary to the Pancreas, ROBERTS.BAR,2003
edited by ANDREA DUNAIF, JEFFREY R. CHANG, Type I Diabetes: Etiology and Treatment, edited
STEPHENFRANKS,ANDRICHARDS.LEGRO,2008 byMARKA.SPERLING,2003
TheMetabolicSyndrome:Epidemiology,Clinical Handbook of Diagnostic Endocrinology, edited
Treatment, and Underlying Mechanisms, byJANETE.HALLANDLYNNETTEK.NIEMAN,2003
Pediatric Endocrinology: A Practical Clinical
edited by BARBARA C. HANSEN AND GEORGE
A.BRAY,2008 Guide,editedbySALLYRADOVICKANDMARGARET
Genomics in Endocrinology: DNA Microarray H.MACGILLIVRAY,2003
AnalysisinEndocrineHealthandDisease, DiseasesoftheThyroid,SecondEdition,editedby
edited by STUART HANDWERGER AND BRUCE J. LEWISE.BRAVERMAN,2003
DevelopmentalEndocrinology:FromResearchto
ARONOW,2008
Controversies in Treating Diabetes: Clinical and ClinicalPractice,editedbyERICAA.EUGSTER
Research Aspects, edited by DEREKLEROITH ANDORAHIRSCHPESCOVITZ,2002
Osteoporosis: Pathophysiology and Clinical
ANDAARONI.VINIK,2007
AutoimmuneDiseasesinEndocrinology,editedby Management, edited by ERICS. ORWOLLAND
ANTHONYP.WEETMAN,2007 MICHAELBLIZIOTES,2002
When Puberty is Precocious: Scientific and Challenging Cases in Endocrinology, edited by
ClinicalAspects,editedbyORAH.PESCOVITZ MARKE.MOLITCH,2002
Selective Estrogen Receptor Modulators:
ANDEMILYC.WALVOORD,2007
ResearchandClinicalApplications,edited
Hypertension and Hormone Mechanisms, edited
byROBERTM.CAREY,2007 by ANDREA MANNI AND MICHAEL F. VERDERAME,
2002
Insulin Resistance and Polycystic Ovarian
Syndrome: Pathogenesis, Evaluation Transgenics in Endocrinology, edited by MARTIN
and Treatment, edited by JOHNE. NESTLER, MATZUK, CHESTER W. BROWN, AND T. RAJENDRA
KUMAR,2001
EVANTHIADIAMANTI-KANDARAKIS,RENATOPASQUALI,
Assisted Fertilization and Nuclear Transfer in
ANDD.PANDIS,2007
Mammals, edited by DONP. WOLFANDMARY
TheLeydigCellinHealthandDisease,editedby
ZELINSKI-WOOTEN,2001
ANITA H. PAYNE AND MATTHEW PHILLIP HARDY, Adrenal Disorders, edited by ANDREW N.MARGIORIS
2007
ANDGEORGEP.CHROUSOS,2001
Treatment of the Obese Patient, edited by ROBERT Endocrine Oncology, edited by STEPHENP. ETHIER,
F.KUSHNERANDDANIELH.BESSESEN,2007 2000
AndrogenExcessDisordersinWomen:Polycystic Endocrinology of the Lung: Development and
Ovary Syndrome and Other Disorders, Surfactant Synthesis, edited by CAROLE
Second Edition, edited by RICARDO AZZIS, R.MENDELSON,2000
JOHNE.NESTLER,ANDDIDIERDEWAILLY,2006 SportsEndocrinology,editedbyMICHELLEP.WARREN
Evidence-Based Endocrinology, edited by VICTOR ANDNAAMAW.CONSTANTINI,2000
M.MONTORI,2006 Gene Engineering in Endocrinology, edited by
Office Andrology, edited by PHILLIPE.PANTTONAND MARGARETA.SHUPNIK,2000
DAVIDE.BATTAGLIA,2005 EndocrinologyofAging,editedbyJOHNE.MORLEY
Stem Cells in Endocrinology, edited by LINDAB. ANDLUCRETIAVANDENBERG,2000
LESTER,2005 HumanGrowthHormone:ResearchandClinical
Male Hypogonadism: Basic, Clinical, and Practice,editedbyROYG.SMITHANDMICHAEL
TherapeuticPrinciples,editedbySTEPHENJ. O.THORNER,2000
WINTERS,2004 Hormones and the Heart in Health and Disease,
AndrogensinHealthandDisease,editedbyCARRIE editedbyLEONARDSHARE,1999
BAGATELLANDWILLIAMJ.BREMNER,2003 Menopause: Endocrinology and Management,
Endocrine Replacement Therapy in Clinical edited by DAVID B. SEIFER AND ELIZABETH
Practice,editedbyA.WAYNEMEIKLE,2003 A.KENNARD,1999
Genomics
in
Endocrinology
DNA Microarray Analysis
in Endocrine Health and Disease
Edited by
tuart Handwerger, md
S
Cincinnati Children’s Hospital Medical Center (CCHMC),
University of Cincinnati College of Medicine, Cincinnati, OH, USA
ruce ronow p d
B J. A ,
h
University of Cincinnati College of Medicine, Cincinnati, OH, USA
Editors
StuartHandwerger BruceAronow
CincinnatiChildren’sHospitalMedical UniversityofCincinnatiCollegeofMedicine
Center(CCHMC) Cincinnati,OH,USA
UniversityofCincinnatiCollegeofMedicine
3333BurnettAvenue
Cincinnati,OH45229,USA
[email protected]
SeriesEditor
P.MichaelConn,MD
DivisionofNeuroscience
OregonHealthandScienceUniversity
OregonNationalPrimateResearchCenter
505NW185thAve.
Beaverton,OR97006,USA
ISBN:978-1-58829-651-1 e-ISBN:978-1-59745-309-7
LibraryofCongressControlNumber:2007931072
©2008HumanaPress,apartofSpringerScience+BusinessMedia,LLC
Allrightsreserved.Thisworkmaynotbetranslatedorcopiedinwholeorinpartwithoutthewrittenpermissionof
thepublisher(HumanaPress,999RiverviewDrive,Suite208,Totowa,NJ07512USA),exceptforbriefexcerptsin
connectionwithreviewsorscholarlyanalysis.Useinconnectionwithanyformofinformationstorageandretrieval,
electronicadaptation,computersoftware,orbysimilarordissimilarmethodologynowknownorhereafterdeveloped
isforbidden.
Theuseinthispublicationoftradenames,trademarks,servicemarks,andsimilarterms,eveniftheyarenotidentified
assuch,isnottobetakenasanexpressionofopinionastowhetherornottheyaresubjecttoproprietaryrights.
Coverillustration:Acompositeofacomplexgeneexpressionprofileheatmap,anetworkviewofgeneinteractions
thatconstitutethemechanismsforgeneregulation,andacartoonviewofendocrineandparacrinerelationshipswithin
andbetweendifferentendocrinetissuesandsomatictissuesrespondingtoendocrinehormones.Theheatmapdepicts
clustersofgenes(inrows)thatarecoordinatelyactivated(red)orrepressed(blue)indifferenttissuesandasafunction
ofdifferentinfluences(samplesandtreatmentsareincolumnsacrossthemap)suchasbydifferentcombinationsof
hormonalagents.(CourtesyofMikeZenderandBruceAronow.)
Printedonacid-freepaper
987654321
springer.com
Preface
Duringthelastfiveyears,thedevelopmentofnewtechnologiescapableofmonitoring
genome function has gone from hopeful estimates to very solid depictions of genome
output from individual samples. The application of this technology to the fields of
endocrinologyhasresultedinnewinsightsaswellastherecognitionthatrefinementsin
biological sampling, technology, experimentation, and data analysis and interpretation
will yield a wealth of new understandings. In this volume, forty-five plus authors have
contributed descriptions of a variety of investigations that reflect the beginnings of
an integrated understanding of how different biological systems respond to endocrine
signals.Thedevelopmentandapplicationoffocusedstudiesthatcanrevealthemecha-
nisms of endocrine action is a major and exciting challenge. Endocrine actions are
divided over a broad range of mechanisms that encompass development, homeostasis,
reproduction,andenvironmentaladaptivenessofcells,tissues,systems,andorganisms.
Givenadequateexperimentaldesignandanalysis,geneexpressionprofilingcanprovide
considerable insight into endocrine system functions, responses, and interactions.
In our introductory chapter, we describe several issues in hypothesis formulation,
experimentaldesign,dataanalysis,andfollow-upstudiesthatmaycorroborate,validate,
and extend hypotheses gained through microarray analyses. The contributed chapters
spanavarietyofapplicationsthatwehavedividedintotheareasof(1)genomicinsights
into molecular mechanisms responsible for hormone action, (2) genomic characteri-
zations of endocrine producing tissues, and (3) genomic manifestations of diseases of
hormonal systems.
We thank all of the authors for their efforts in summarizing some of their current
understandingsandtothemembersofourdepartmentsandinstitutionwhohaveshown
patience and provided support for our efforts. We would also like to thank Humana
Press for their enthusiasm on this project, and Allene Ford and Nancy Fehr for their
invaluable assistance.
Stuart Handwerger
Bruce J. Aronow
v
Contents
Preface..................................................... v
Contributors................................................ ix
Part I Introduction
1 Microarray-based Gene Expression Analysis of Endocrine
Systems: Principles of Experimental Design and Interpretation
Anil G. Jegga, DVM, Bruce J. Aronow, PhD,
and Stuart Handwerger, MD.............................. 3
Part II Hormone Action and Molecular Mechanisms
2 Gene Expression Profiles and Transcription Factors Involved
in Parathyroid Hormone Signaling in Osteoblastic Cells
Ling Qin, PhD, Ping Qiu, PhD, and Nicola C.
Partridge, PhD........................................... 25
3 Analysis of Growth Hormone Effects on Hepatic Gene
Expression in Hypophysectomized Rats
Amilcar Flores-Morales, PhD and
Leandro Fernández-Pérez, MD, PhD....................... 41
4 Gene Expression Profiling in Leiomyoma in Response to GnRH
Therapy and TGF-(cid:2)
Nasser Chegini, PhD and Xiaoping Luo, MD................. 67
5 Gene Profiling Analysis of Androgen Receptor Mediated
Function
Clay E. S. Comstock, PhD, Craig J. Burd, PhD,
Walter J. Jessen, PhD, and Karen E. Knudsen, PhD......... 83
6 Interrogating Estrogen Receptor (cid:3) Signaling in Breast Cancer
by Chromatin Immunoprecipitation Microarrays
Alfred S. L. Cheng, PhD, Huey-Jen L. Lin, PhD,
and Tim H. -M. Huang, PhD.............................. 115
7 Gene Expression Analysis of the Adrenal Cortex in Health
and Disease
Anelia Horvath, PhD and Constantine A. Stratakis, MD,
DMedSci................................................. 131
Part III Endocrine Producing Tissues
8 DNA Microarray Analysis of Human Uterine Decidualization
Ori Eyal, MD and Stuart Handwerger, MD.................. 147
vii
viii Contents
9 Large-scale DNA Microarray Data Analysis Reveals
Glucocorticoid Receptor-mediated Breast Cancer Cell
Survival Pathways
Min Zou, PhD, Wei Wu, MD, PhD,
and Suzanne D. Conzen, MD.............................. 165
10 Application of Microarrays for Gene Transcript Analysis
in Type 2 Diabetes
R. Sreekumar, PhD, C. P. Kolbert, MS, Y. Asmann, PhD,
and K. S. Nair, MD, PhD................................. 185
11 DNA Microarray Analysis of Effects of TSH, Iodide, Cytokines,
and Therapeutic Agents on Gene Expression in Cultured
Human Thyroid Follicles
Kanji Sato, MD, PhD, Kazuko Yamazaki, BS,
and Emiko Yamada, MD.................................. 207
Part IV Diseases of Hormonal Systems
12 Genomics and Polycystic Ovary Syndrome (PCOS): The Use
of Microarray Analysis to Identify New Candidate Genes
Jennifer R. Wood, PhD and Jerome F. Strauss III, MD, PhD... 219
13 Microarray Analysis of Alterations Induced by Obesity in White
Adipose Tissue Gene Expression Profiling
Julien Tirard, Ricardo Moraes, Danielle Naville, PhD,
and Martine Bégeot, PhD................................. 239
14 Novel Molecular Signaling and Classification of Human
Clinically Nonfunctioning Pituitary Adenomas Identified
by Microarray and Reverse Transcription-Quantitative
Polymerase Chain Reaction
Chheng-Orn Evans, MS, Carlos S. Moreno, PhD,
and Nelson M. Oyesiku, MD, PhD, FACS .................. 263
15 Gene Expression Studies of Prostate Hyperplasia in Prolactin
Transgenic Mice
Karin Dillner, PhD, Jon Kindblom, MD, PhD, Amilcar
Flores-Morales, PhD, and Håkan Wennbo, MD, PhD....... 271
Index.......................................................... 283
Contributors
Bruce J. Aronow, phd, Division Biomedical Informatics, Cincinnati Children’s
Hospital Medical Center, Cincinnati, Ohio, USA Department of Pediatrics,
University of Cincinnati College of Medicine, Cincinnati, OH
Yan W. Asmann, phd, Bioinformatics Application Scientist, Mayo Clinic College
of Medicine, Rochester, MN
Martine Bégeot, phd, Permanent Researcher from INSERM, Lyon, France
Craig J. Burd, phd, Departments of Cell Biology and Pathology, University of
Cincinnati, Cincinnati, OH
Nasser Chegini, phd, Professor, Division of Reproductive Endocrinology
and Infertility, Department of Obstetrics and Gynecology, University of Florida
College of Medicine, Gainesville, FL
Alfred S. L. Cheng, phd, Post-doctoral Researcher, Division of Human Cancer
Genetics, Department of Molecular Virology, Immunology, and Medical Genetics,
Comprehensive Cancer Center, Ohio State University, Columbus, OH
Clay E. S. Comstock, phd, Vontz Center for Molecular Studies, University of
Cincinnati, Cincinnati, OH
Suzanne D. Conzen, md, Associate Professor, Department of Medicine and The
Ben May Institute of Cancer Research, The University of Chicago, Chicago, IL
Karin Dillner, phd, Disease Biology, AstraZeneca R&D, Södertälje, Sweden
Chheng-Orn Evans, ms, Research Supervisor, Department of Neurosurgery, Emory
University, Atlanta, GA
Ori Eyal, md, The Edmond and Lily Safra Children’s Hospital, The Chaim Sheba
Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Hashomer,
Israel
Leandro Fernández-Pérez, md, phd, Associate Professor or Pharmacology,
Department of Clinical Sciences, Molecular Pharmacology Group, University
of Las Palmas de Gran Canaria–Canary Institute for Cancer Research, RTICCC,
Canary Islands, Spain
Amilcar Flores-Morales, phd, Associate Professor of Experimental
Endocrinology, Department of Molecular Medicine and Surgery, Karolinska
Instututet, Karolinska Hospital, Stockholm, Sweden
Stuart Handwerger, md, Division of Endocrinology, Cincinnati Children’s
Hospital Medical Center, Cincinnati, Ohio, USA Department of Pediatrics,
University of Cincinnati College of Medicine, Cincinnati, OH
Anelia Horvath, phd, Senior Fellow, Section on Endocrinology and Genetics,
(SEGEN)/DEB, NICHD, NIH, Bethesda, MD
Tim H. -M. Huang, phd, Professor, Division of Human Cancer Genetics, Department
of Molecular Virology, Immunology, and Medical Genetics, Comprehensive
Cancer Center, Ohio State University, Columbus, OH
ix
x Contributors
Anil G. Jegga, dvm, Division of Biomedical Informatics, Cincinnati Children’s
Hospital Medical Center, Cincinnati, Ohio, USA Department of Pediatrics,
University of Cincinnati College of Medicine, Cincinnati, OH
Walter J. Jessen, phd, Division of Biomedical Informatics, Cincinnati Children’s
Hospital Medical Center, Cincinnati, OH
Jon Kindblom, md, phd, Department of Oncology, Göteborg University, Göteborg,
Sweden
Karen E. Knudsen, phd, Center for Environmental Genetics and Department of Cell
Biology, University of Cincinnati, Cincinnati, OH
Christopher P. Kolbert, ms, Senior Research Technologist, Mayo Clinic College
of Medicine, Rochester, MN
Huey-Jen L. Lin, phd, Assistant Professor, Division of Medical Technology, School
of Allied Medical Professions, Ohio State University, Columbus, OH
Xiaoping Luo, md, Research Assistant Professor, Division of Reproductive
Endocrinology and Infertility, Department of Obstetrics and Gynecology,
University of Florida College of Medicine, Gainesville, FL
Ricardo Moraes, Post-Graduate Student, Breast Center, Baylor College
of Medicine, Houston, TX
Carlos S. Moreno, phd, Assistant Professor, Department of Pathology and
Laboratory of Medicine and Cancer Institute, Emory University, Atlanta, GA
K. Sreekumaran Nair, md, phd, David Murdock Dole Professor and Professor
of Medicine, Division of Endocrinology, Mayo Clinic and Foundation,
Rochester, MN
Danielle Naville, phd, Permanent Researcher from INSERM, Lyon, France
Nelson M. Oyesiku, md, phd, facs, Professor and Vice-Chairman, Neurological
Surgery; Director, Neurosurgery Residency Program; Director, Laboratory
of Molecular Neurosurgery and Biotechnology, Department of Neurological
Surgery, Emory University School of Medicine; Past-President, Congress of
Neurological Surgeons; Past-President, Georgia Neurosurgical Society, Atlanta,
GA
Nicola C. Partridge, phd, Professor and Chair, Department of Physiology
and Biophysics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ
Ling Qin, phd, Assistant Professor, Department of Physiology and Biophysics,
UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ
Ping Qiu, phd, Principal Scientist, Bioinformatics Group and Discovery Technology
Department, Schering-Plough Research Institute, Kenwilworth, NJ
Kanji Sato, md, phd, Professor, Field of Thyroid and Parathyroid Disease, Division
of Internal Medicine, Graduate School of Medicine, Tokyo Women’s Medical
University, Shinjuku-ku, Tokyo, Japan
Raghavakaimal Sreekumar, phd, Associate Professor of Medicine, Mayo Clinic
College of Medicine, Rochester, MN
Constantine A. Stratakis, md, dmedsci, Chief, Heritable Disorders Branch,
NICHD, NIH; Director, Pediatric Endocrinology Training Program, NICHD, NIH;
Head, Section on Endocrinology and Genetics, (SEGEN)/DEB, NICHD, NIH,
Bethesda, MD
Contributors xi
Jerome F. Strauss III, md, phd, Executive Vice President for Medical Affairs, VCU
Health System Dean, Professor of Obstetrics and Gynecology, Virginia
Commonwealth University School of Medicine, Richmond, VA
Julien Tirard, Graduate Student, INSERM, Lyon, France
Hakan Wennbo, md, phd, Integrative Pharmacology, AstraZeneca R&D, Molndal,
Sweden
Jennifer R. Wood, phd, Assistant Professor, Department of Animal Science,
University of Nebraska, Lincoln, NE
Wei Wu, md, phd, Research Associate, Division of Molecular Oncology, Evanston
Northwestern Healthcare Research Institute, Evanston, IL
Emiko Yamada, md, Director, Thyroid Disease Institute, Kanaji Hospital, Kita-ku,
Tokyo, Japan
Kazuko Yamazaki, bs, Thyroid Disease Institute, Kanaji Hospital, Kita-ku, Tokyo,
Japan
Min Zou, phd, Post-doctoral Scholar, Department of Medicine, The University
of Chicago, Chicago, IL
